El papel del antígeno prostático específico (PSA) y el estadio patológico antes de la radioterapia en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con recidiva del cancer de próstata tras prostatectomía radical / Role of PSA levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy

Objetivo Evaluar el valor del antígeno prostático específico (PSA) en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con cáncer de próstata (CaP) de alto (puntuación de Gleason≥8, pT≥3, pN1) y bajo grado (puntuación de Gleason<8, pT<3, pN0). Materiales y métodos Ciento ochenta y ocho pacientes se sometieron a una RMmp de 1,5-T después de la prostatectomía radical y antes de la radioterapia. Los pacientes se dividieron en 2 grupos: el grupo A incluía pacientes con recidiva bioquímica (RB) y el grupo B pacientes sin RB pero con alto riesgo de recidiva local. Teniendo en cuenta la puntuación de Gleason, pT y pN como variables de agrupación independientes, se realizaron análisis ROC de los niveles de PSA en el momento del diagnóstico del CaP primario y antes de la radioterapia con el fin de identificar el punto de corte óptimo para predecir el resultado de la RMmp. Resultados En los grupos A y B, el área bajo la curva del PSA antes de la radioterapia fue superior a la del PSA en el momento del diagnóstico del CaP, en tumores de bajo y alto grado. Para los tumores de bajo grado, la mejor área bajo la curva fue de 0,646 y 0,685 en el grupo A y B, respectivamente; para los tumores de alto grado, la mejor área bajo la curva fue de 0,705 y 1 en el grupo A y B, respectivamente. Para los tumores de bajo grado, el punto de corte óptimo del PSA fue de 0,565-0,58ng/ml en el grupo A (sensibilidad y especificidad: 70,5% y 66%), y de 0,11-0,13ng/ml en el B (sensibilidad y especificidad: 62,5% y 84,6%). Para los tumores de alto grado, el punto de corte de PSA óptimo fue de 0,265-0,305ng/ml en el grupo A (sensibilidad y especificidad: 95% y 42,1%), y de 0,13-0,15ng/ml en el grupo B (sensibilidad y especificidad: 100%). Conclusión La RMmp se debe realizar como herramienta diagnóstica complementaria siempre que se detecte una RB, especialmente en el CaP de alto grado... (AU)

Objective To evaluate prostate-specific antigen (PSA) value in multiparametric magnetic resonance imagin (mp-MRI) results prediction, analyzing patients with high (Gleason Score ≥8, pT≥3, pN1) and low grade (Gleason Score <8, pT<3, pN0) prostate cancer (PCa). Materials and methods One hundred eighty-eight patients underwent 1.5-T mp-MRI after radical prostatectomy and before radiotherapy. They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score, pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before radiotherapy were performed in order to identify the optimal cut-off to predict mp-MRI result. Results Group A and B showed higher area under the curve for PSA before radiotherapy than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best area under the curve was 0.646 and 0.685 in group A and B; for high grade the best area under the curve was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/ml in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/ml in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/ml in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/ml in B (sensitivity, specificity: 100%). Conclusion Mp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/ml. (AU)

Robot-assisted partial nephrectomy using the novel Hugo™ RAS system: Feasibility, setting and perioperative outcomes of the first off-clamp series.

INTRODUCTION: Hugo Robot-Assisted Surgery (RAS) System has been conceived with enhanced modularity but its role for nephron-sparing surgery setting still remains poorly explored. We aimed to describe our experience in robot-assisted partial nephrectomy (RAPN) with a three-arms setting for the first off-clamp series using the new Hugo RAS System. METHODS: Patients were placed on an extended flank position at the margin of the surgical bed with a slightly flexion (45°). The first 11 mm robotic trocar (camera port) was placed along the pararectal line 14 ± 2 cm far from the umbilicus. The pneumoperitoneum was then induced through the AirSeal system (SurgiQuest, Milford, Connecticut, USA©). Two more 8 mm operative robotic ports were placed under direct vision, either 8 ± 1 cm far from optic's port. Two 12 mm laparoscopic ports for bed-assistant were placed between robotic ports. Monopolar curved shears, fenestrated grasper, and large needle driver were used in a three-instruments configuration. RESULTS: Off-clamp RAPN was successfully performed in seven patients with cT1 renal masses using a trans-peritoneal route. Median port placement and docking time was 6 min (IQR, 4-8 min). Hemostasis was achieved through renorraphy using a single transfix stitch with sliding clips technique. There was no need for additional ports placement. No intraoperative complications occurred, no clashing of robotic instruments or between the robotic arms was observed. No technical failures of the system occurred. Median console time was 83 min (IQR, 68-115 min). Median estimated blood loss were 200 ml (IQR, 50-400 ml). All patients were discharged between post-operative day 2 and 3, without the need of hospital readmission. No complications were recorded within the first 30 post-operative days. CONCLUSIONS: We performed the first series of off-clamp RAPN using the novel HUGO RAS System. This novel robotic platform showed an easy-friendly docking system, providing excellent perioperative outcomes with a simple three-arms configuration.

Role of psa levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy.

OBJECTIVE: To evaluate PSA value in mp-MRI results prediction, analyzing patients with high (GS≥8, pT≥3, pN1) and low grade (GS<8, pT<3, pN0) Prostate Cancer (PCa). MATERIALS AND METHODS: One hundred eighty-eight patients underwent 1.5-Tmp-MRI after Radical Prostatectomy (RP) and before Radiotherapy (RT). They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score (GS), pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before RT were performed in order to identify the optimal cut-off to predict mp-MRI result. RESULTS: Group A and B showed higher AUC for PSA before RT than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best AUC was 0.646 and 0.685 in group A and B; for high grade the best AUC was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/mL in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/mL in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/mL in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/mL in B (sensitivity, specificity: 100%). CONCLUSION: Mp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/mL.

Impact of a delayed presentation to the emergency department for acute renal colic on biochemical and clinical outcomes.

INTRODUCTION AND OBJECTIVE: To verify the impact of delay on biochemical and clinical outcomes for patients presenting to the emergency department (ED) with acute renal colic. MATERIALS AND METHODS: Data were retrospectively collected from three institutions of two European countries between 01 January and 30 April 2020. Patients who presented to the ED with unilateral or bilateral renal colic caused by urolithiasis confirmed by imaging tests during the study period were included. A presentation after 24 h since the onset of symptoms was considered a delay. Patients presenting before 24 h from the symptom onset were included in Group A, while the patients presenting after 24 h in Group B. Clinical and biochemical parameters and management were compared. RESULTS: A total of 397 patients who presented to ED with confirmed urolithiasis were analyzed (Group A, n = 199; Group B, n = 198. The median (IQR) delay in presentation was 2 days (1,5-4). At presentation, no statistically significant differences were found amongst the two groups of patients regarding presenting symptoms such as fever and flank pain, and the median serum levels of creatinine, C reactive protein and white blood cells. No differences were found in terms of conservative or operative management. CONCLUSION: Delay in consultation >24 h is not associated with worsening biochemical parameters and clinical outcomes. Most patients with acute loin pain do not necessarily need urgent attendance to the ED and may be managed in the outpatients.

El papel de la resonancia magnética multiparamétrica en el diagnóstico de la recidiva local tras la prostatectomía radical y antes de la radioterapia de rescate / The role of multiparametric magnetic resonance imaging in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy

Objetivo Evaluar la precisión diagnóstica de la resonancia magnética multiparamétrica (RMmp) en la detección de la recidiva local del cáncer de próstata (CaP) después de la prostatectomía radical (PR) y antes de la radioterapia (RT). Materiales y métodos Un total de 188 pacientes se sometieron a una RMmp de 1,5T después de la PR y antes de la RT. Los pacientes se dividieron en 2 grupos: con recidiva bioquímica (grupo A) y sin recidiva bioquímica, pero con alto riesgo de recidiva local (grupo B). Las variables continuas se compararon entre los 2 grupos mediante la prueba t de Student; las variables categóricas se analizaron mediante chi-cuadrado de Pearson. El análisis ROC se realizó considerando como variables de agrupación el PSA antes de la RT, el grado ISUP, el pT y el pN. Resultados La recidiva del CaP (reducción de los niveles de PSA después de la RT) fue del 89,8% en el grupo A y del 80,3% en el grupo B. Al comparar los pacientes con y sin recidiva del CaP, hubo una diferencia significativa en los valores de PSA antes de la RT para el grupo A, y en los valores de PSA antes y después de la RT para el grupo B. En el grupo A hubo una correlación significativa entre el PSA antes de la RT y el diámetro de la recidiva, y entre el PSA antes de la RT y el tiempo transcurrido hasta la recidiva. La precisión diagnóstica de la RMmp en la detección de la recidiva local del CaP tras la RT es del 62,2% en el grupo A y del 38% en el grupo B. La imagen potenciada en difusión es la secuencia de RM más específica y la perfusión dinámica con contraste la más sensible. Para el PSA=0,5ng/ml, el AUC disminuye, mientras que la sensibilidad y la precisión aumentan para cada secuencia de RM. Para el PSA=0,9ng/ml, el AUC de la perfusión dinámica con contraste aumenta significativamente (AU)

Purpose Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of prostate cancer (PCa) after radical prostatectomy (PR) and before radiation therapy (RT). Materials and methods A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into 2 groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between 2 groups using Student-t test; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. Results PCa recurrence (reduction of PSA levels after RT) was 89.8% in group A and 80.3% in group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. Diffusion weighted imaging is the most specific MRI-sequence and dynamic contrast enhanced the most sensitive. For PSA=0.5ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA=0.9ng/ml, dynamic contrast enhanced-AUC increases significantly. Conclusion mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of diffusion weighted imaging for PSA≤0.5ng/ml (AU)

The role of multiparametric mri in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy.

PURPOSE: Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of Prostate Cancer (PCa) after Radical Prostatectomy (PR) and before Radiation Therapy (RT). MATERIALS AND METHODS: A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into two groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between two groups using T-Student; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. RESULTS: PCa recurrence (reduction of PSA levels after RT) was 89.8% in the group A and 80.3% in the group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. DWI is the most specific MRI-sequence and DCE the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, DCE-AUC increases significantly. CONCLUSION: mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of DWI for PSA ≤ 0.5 ng/ml.

Exploring the Residents' Perspective on Smart learning Modalities and Contents for Virtual Urology Education: Lesson Learned During the COVID-19 Pandemic. / Explorando la perspectiva de los residentes sobre las modalidades y contenidos de aprendizaje inteligente para la educación virtual de urología: lección aprendida durante la pandemia de la COVID-19.

PURPOSE: The COVID-19 outbreak has substantially altered residents' training activities. While several new virtual learning programs have been recently implemented, the perspective of urology trainees regarding their usefulness still needs to be investigated. METHODS: A cross-sectional, 30-item, web-based Survey was conducted through Twitter from April 4th, 2020 to April 18th, 2020, aiming to evaluate the urology residents' perspective on smart learning (SL) modalities (pre-recorded videos, webinars, podcasts, and social media [SoMe]), and contents (frontal lessons, clinical case discussions, updates on Guidelines and on clinical trials, surgical videos, Journal Clubs, and seminars on leadership and non-technical skills). RESULTS: Overall, 501 urology residents from 58 countries completed the survey. Of these, 78.4, 78.2, 56.9 and 51.9% of them considered pre-recorded videos, interactive webinars, podcasts and SoMe highly useful modalities of smart learning, respectively. The contents considered as highly useful by the greatest proportion of residents were updates on guidelines (84.8%) and surgical videos (81.0%). In addition, 58.9 and 56.5% of responders deemed seminars on leadership and on non-technical skills highly useful smart learning contents. The three preferred combinations of smart learning modality and content were: pre-recorded surgical videos, interactive webinars on clinical cases, and pre-recorded videos on guidelines. CONCLUSION: Our study provides the first global «big picture¼ of the smart learning modalities and contents that should be prioritized to optimize virtual Urology education. While this survey was conducted during the COVID-19 outbreak, our findings might have even more impact in the future.

[-2]proPSA versus ultrasensitive PSA fluctuations over time in the first year from radical prostatectomy, in an high-risk prostate cancer population: A first report.

BACKGROUND: [-2]proPSA and its derivatives have an higher diagnostic accuracy than PSA in predicting prostate cancer (PCa). In alternative to PSA, ultrasensitive PSA (uPSA) and [-2]proPSA could be potentially useful in recurrent disease detection. This research focused on [-2]proPSA and uPSA fluctuations over time and their possible clinical and pathological determinants, in the first year after RP. METHODS: A cohort of 106 consecutive patients, undergoing RP for high-risk prostate cancer (pT3/pT4 and/or positive margins), was enrolled. No patient received either preoperative/postoperative androgen deprivation therapy or immediate adjuvant RT, this latter for patient choice. [-2]proPSA and uPSA were measured at 1, 3, 6, 9, 12 months after RP; their trends over time were estimated by the mixed-effects linear model. The uPSA relapse was defined either as 3 rising uPSA values after nadir or 2 consecutive uPSA >0.2 ng/ml after RP. RESULTS: The biochemical recurrence (BCR) rate at 1 year after RP was either 38.6 % (in case of 3 rising uPSA values) or 34.9 % (in case of PSA >0.2 ng/ml after nadir), respectively. The main risk factors for uPSA fluctuations over time were PSA at diagnosis >8 ng/ml (p = 0.014), pT (p = 0.038) and pN staging (p = 0.001). In turn, PSA at diagnosis >8 ng/ml (p = 0.012) and pN (p < 0.001) were the main determinants for [-2]proPSA trend over time. In a 39 patients subgroup, uPSA decreased from month 1 to 3, while [-2]proPSA increased in 90 % of them; subsequently, both uPSA and [-2]proPSA increased in almost all cases. The [-2]proPSA trend over time was independent from BCR status either in the whole cohort as well in the 39 men subgroup. CONCLUSIONS: Both uPSA and [-2]proPSA had independent significant fluctuations over time. PSA at diagnosis >8 ng/ml and pathological staging significantly modified both these trends over time. Since BCR was not confirmed as determinant of [-2]proPSA fluctuations, its use as marker of early biochemical relapse may not be actually recommended, in an high-risk prostate cancer patients population.

Safety and Efficacy of Bipolar Versus Monopolar Transurethral Resection of the Prostate in Patients with Large Prostates or Severe Lower Urinary Tract Symptoms: Post Hoc Analysis of a European Multicenter Randomized Controlled Trial.

PURPOSE: We compare bipolar vs monopolar transurethral prostate resection safety/secondary outcomes including efficacy in patients with large prostate volume or severe lower urinary tract symptoms. MATERIALS AND METHODS: From July 2006 to June 2009 candidates for transurethral prostate resection were recruited at 4 centers, randomized 1:1 into monopolar/bipolar transurethral prostate resection arms and followed up to 36 months. Post hoc data analysis from patients with large prostate volume or severe lower urinary tract symptoms is presented. Patients with large prostate volume or severe lower urinary tract symptoms were defined as those with transrectal ultrasound based prostate volume greater than 80 ml or International Prostate Symptom Score greater than 19. Safety was estimated using sodium/hemoglobin changes immediately after surgery, complications during the early postoperative period (up to 6 weeks), and short-term (up to 12 months) and midterm (up to 36 months) followup. Secondary outcomes included, among others, efficacy quantified by changes in maximum urine flow rate, post-void residual urine volume and International Prostate Symptom Score compared with baseline. RESULTS: A total of 279 patients were randomized. Post hoc analysis of data from patients with a large prostate volume or severe lower urinary tract symptoms was based on analysis A-in 62 of 279 participants (22.3%) (monopolar transurethral prostate resection 32, bipolar transurethral prostate resection 30) or analysis B-in 126 of 279 participants (45.2%) (monopolar transurethral prostate resection 57, bipolar transurethral prostate resection 69). Mean (SD) prostate volume was 108.0 (25.9) ml for monopolar transurethral prostate resection and 108.9 (23.4) ml for bipolar transurethral prostate resection (p=0.756). Mean International Prostate Symptom Score was 25.0 (4.2) for monopolar transurethral prostate resection and 25.3 (3.7) for bipolar transurethral prostate resection (p=0.402). Neither safety nor any secondary outcome differed significantly between the arms throughout followup. The only exception was the decrease in sodium (analysis A), which was significantly greater after monopolar transurethral prostate resection (-4.2 vs -0.7 mmol/l, p=0.023) and did not translate into a significant difference in transurethral resection syndrome rates (monopolar transurethral prostate resection 1 of 32 vs bipolar transurethral prostate resection 0 of 30, p=1.000). CONCLUSIONS: Bipolar and monopolar transurethral prostate resection show similar safety/efficacy in these patient subpopulations.

Does nephrectomy during radical adrenalectomy for stage II adrenocortical cancer affect patient outcome?

PURPOSE: To evaluate if including nephrectomy in the standard surgical approach to stage II adrenocortical cancer (i.e., adrenalectomy) might modify oncologic outcome of patients. METHODS: We performed a retrospective analysis involving 41 patients with stage II adrenocortical cancer (ACC) who had undergone radical surgery. Patients were divided into two groups according to the surgical procedure: group A = radical adrenalectomy alone, group AN = radical adrenalectomy + radical nephrectomy. Oncologic effectiveness of the procedures was tested comparing the recurrence-free and overall survival of patients of A vs AN groups. RESULTS: The group A consisted of 25 patients and group AN of 16 patients. No differences were noted between the two groups in terms of demographic data and ACC characteristics. During follow-up, 15/25 (60 %) patients of group A vs 14/16 (87.5 %) patients of group AN experienced a recurrence, after a median of 36 months in group A and 10 months in group AN (p = 0.06); a significant impairment of renal function was recorded in patients of AN group with respect to those of group A. Finally, 13/25 (52 %) patients of group A and 10/16 (62.5 %) patients of group AN died due to ACC-related causes. No differences in survival times were noted (p = 0.3). CONCLUSION: Our study suggests that adjunctive nephrectomy does not modify the oncologic results of adrenalectomy in the treatment of stage II ACC in terms of recurrence-free and overall survival. Thus, when there are no signs of ACC local invasion, surgeon should make every effort to preserve the kidney.

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease.

Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n=51) had higher tumor load in bone (P=0.005), higher plasma chromogranin A (CgA, P=0.01), serum alkaline phosphatase (P=0.01), urinary N-telopeptide (NTX, P=0.002) and lower hemoglobin values (P=0.01), while hypercalcemic patients (n=16) had higher plasma CgA (P=0.001) and serum lactate dehydrogenase values (P=0.001), higher bone pain (P=0.003) and a lower frequency of pure osteoblastic lesions (P=0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P=0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1-6.8, P=0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.

Proposal of an improved prognostic classification for pT3 renal cell carcinoma.

PURPOSE: The prognostic accuracy of the current TNM 2002 staging system for locally advanced renal cell carcinoma has been questioned. To contribute to the development of a more accurate classification for this stage of disease we assessed the correlation between patterns of invasion in the pT3 category and outcomes in a large multi-institutional series. MATERIALS AND METHODS: Pathological data and clinical followup on 513 pT3 renal cell carcinoma cases treated with radical nephrectomy between 1983 and 2005 at 3 Italian academic centers were retrospectively reviewed. Cause specific survival rates were calculated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Estimated overall 5-year cause specific survival was 50.1% at a median followup of 61.5 months in survivors. The current TNM classification was not a significant outcome prognosticator. Patients with a tumor invading only the perirenal or sinus fat were at lowest risk for death from the disease. Patients at intermediate risk had tumors with invasion of the venous system alone. Simultaneous perirenal fat and sinus fat invasion or perirenal fat and vascular invasion as well as adrenal gland involvement characterized high risk tumors. Low risk tumors could be further divided into 2 groups with different outcomes based on a size cutoff of 7 cm. Our classification was a significant predictor of survival on multivariate analysis as well as M stage, N stage, Fuhrman grade and tumor size. CONCLUSIONS: We confirm that the prognostic usefulness of the current 2002 TNM system for pT3 renal cell carcinoma is limited. We have identified 4 groups of tumors with distinct patterns of invasion and significantly different survival probabilities in this category. Large prospective series are needed to validate these findings.

[Tadalafil versus sildenafil citrate in the treatment of ED:Italian patients' preferences and explanatory notes].

This is an open, multicentre, randomized, crossover study having the aim to evaluate the preference for sildenafil citrate or tadalafil in a population of Italian patients affected by ED, and to compare the efficacy and safety of these two drugs. MATERIAL AND METHODS. From October 2003 to November 2004, thirteen Italian centers enrolled ED patients (age >18) being in steady and naïve relation to ED treatment, both through PDE5 inhibitors and any other treatment option. These patients were randomized to sildenafil or tadalafil for 12 weeks, after which they were switched to the alternative treatment for a further 12 weeks. The preference was evaluated through the Treatment Preference Question (TPQ): "During this clinical trial you have taken tadalafil and sildenafil for the treatment of erectile dysfunction. Which medication do you prefer to take for the next 8 weeks of treatment?". Moreover, patients were asked to express their preference as "strong" or "moderate" and to answer some questions to clarify the reasons behind their preference. SEP and IIEF-EF questionnaires were used for a comparison of efficacy. RESULTS. 167 patients were enrolled, 144 of whom completed both treatment periods. On being asked the TPQ, 75% of patients (n=108) decided to continue treatment with tadalafil, in particular because it made it possible to have an erection many hours after taking the medication (first or second preference reason for 64.8% of patients), while 25% (n=36) preferred sildenafil (p=0.001). Both drugs improved the IIEF-EF and SEP scores compared to baseline, with a slightly but significantly greater improvement with tadalafil for both parameters. CONCLUSIONS. Tadalafil and sildenafil are both effective and well tolerated. Most of the patients prefer tadalafil thanks to the possibility of having sexual intercourse many hours after taking the medication.

Reassessing the current TNM lymph node staging for renal cell carcinoma.

OBJECTIVE: The most commonly used staging system for renal cell carcinoma (RCC) is the tumor-node-metastasis (TNM) system. In the most recent TNM edition, lymph node (LN) involvement is defined as pN0, pN1, or pN2, depending on the number of metastatic LNs (none, 1, or >1). This study evaluated the prognostic value of this classification and tried to improve its clinical impact by considering an additional parameter, that is, LN density (ratio between number of positive LNs and total number of LNs retrieved). METHODS: All pathologic reports of radical nephrectomies performed for RCC in two urologic centers between November 1983 and December 1999 were reviewed. For each patient, complete clinical and pathologic data, number of LNs removed, location and number of positive LNs, and LN density were recorded. The Kaplan-Meyer method and the log-rank test were used to calculate cause-specific survival rates and to compare survival curves, respectively. RESULTS: A total of 735 patients underwent radical nephrectomy. Lymphadenectomy was performed in 618 cases, and the rate of positive LNs was 14.2%. The 5-yr cause-specific survival rate of pN+ patients was 18%, with no statistically significant difference between pN1 and pN2. The average number of LNs removed was 13 (range, 1-35). The median number of LNs involved was 3 (range, 1-18). LN density ranged between 3.7% and 100% (median, 22.9%). The number of LNs removed had no impact on survival in pN+ patients. The only significant unfavorable prognostic factors were >4 LNs involved (p = 0.02) and LN density >60% (p = 0.01). CONCLUSION: The results show that in RCC the current TNM stratification of positive LNs is not significantly correlated with prognosis. From our data it appears that classification as < or =4 or >4 LNs involved, supported by LN density, better reflects the impact of the disease on survival.

Immune response in prostate cancer.

Surprisingly perhaps for a tumor where there is such clear proof of a primary hormonal basis to its development, there is emerging evidence that all elements playing a key role in prostate cancer somehow affect the host immune system. This review turns the spotlight on some previously unsuspectable aspects, able to interact with the immune system in prostate cancer patients PSA, sex hormones, inflammatory infiltrates, cytokines, growth factors, neoformed blood vessels, neurotransmitters and neurotrophins, cigarette smoking, diet, therapeutic approaches. The concept of exploiting the immune system to combat cancer is not new, but only nowadays immunotherapy is a reality. Prostate cancer is an excellent target, involved in an increasing number of clinical immunotherapeutic trials. The main current purpose is to overcome the host immune tolerance of tumor cells. The most recent progresses in gene, monoclonal antibody and vaccine therapies are reported.

Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease.

Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07-1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06-1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials.

Laparoscopic telementored adrenalectomy: the Italian experience.

BACKGROUND: Laparoscopy is widely accepted as the gold standard for adrenalectomy. Telementoring has been developed to reduce the complications associated with surgeon inexperience. We report our preliminary experience with laparoscopic telementored adrenalectomy. METHODS: From July 2002 to May 2003, eight laparoscopic telementored adrenalectomies were performed between two separate operating sites 430 km apart. Six of these procedures were monolateral laparoscopic adrenalectomies, and one was bilateral. All cases were performed by an expert open surgeon who was skilled in laparoscopic procedure but who had no experience in laparascopic adrenalectomy RESULTS: All the procedures were successfully performed in a telementored fashion. The mean operative times, blood loss, and postoperative morbidity results were comparable to those for standard laparoscopic adrenalectomies reported in the literature. CONCLUSIONS: This preliminary experience has demonstrated the feasibility of national telementoring. It is a viable method that can potentially add to surgical education and decrease the likelihood of complications due to inexperience with new techniques.

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease.

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.

Home and office uroflowmetry for evaluation of LUTS from benign prostatic enlargement.

A group of 107 patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE) participated to the HOUSE Study (Home and Office Uroflowmetry Specific Evaluation). Patients received routine investigation, consisting of medical history taking, physical examination including digital rectal examination, prostate-specific antigen (PSA), assessment of symptoms listed both on the International Prostate Symptom Score and on ICS-male questionnaire. We examined the results of uroflowmetry evaluation in this population; data were analysed to observe if any circadian changes of parameters obtained with home uroflowmetry could be detected. We searched a correlation between Q(max), Q(ave) and ICS-benign prostatic hyperplasia symptom score: a significantly inverse correlation was found only for Q(max), confirming Q(max) as a reliable parameter to quantify subjective symptoms. When examining the multiple flow curves recorded in the same patient with home uroflowmetry, voided volume and flow time had usually higher values during night-time: the existence of circadian changes of uroflowmetry parameters in patients with LUTS from BPE was confirmed, and lower values of average and maximum flow rates during sleep hours were recorded in the same patient. In conclusion, when evaluating the natural history or treatment outcome of individual patients or group of patients in clinical trials for evaluation of BPE and LUTS, an assessment including multiple measurements may be useful and of value.

Bilateral adrenalectomy for Cushing's syndrome: a comparison between laparoscopy and open surgery.

We report our experience with bilateral adrenalectomy for treatment of Cushing's syndrome and we compare the outcome of laparoscopy with open surgery in terms of effectiveness and safety. A series of 23 patients underwent bilateral adrenalectomy for treatment of Cushing's syndrome [Cushing's disease in 16, ectopic ACTH syndrome in 2, and ACTH-independent macronodular adrenal hyperplasia (AIMAH) in 5 cases]. From 1993 to 1996, all patients were treated using an open approach (Group A), while from 1997 all patients were treated using a transperitoneal laparoscopic approach (Group B). The comparison between the 2 groups was performed considering patients characteristics, operative times, blood losses, intraoperative and post-operative complications, analgesic consumption, post-operative hospital stay and recovery. Open surgery was performed in 10 patients and laparoscopy in 13 patients. No significant difference was recorded between the two groups as to patients' characteristics and complications. Mean operative time was significantly increased in Group B, while post-operative hospital stay was significantly longer in Group A. Laparoscopic bilateral adrenalectomy can be safely and effectively employed to treat Cushing's syndrome. However, long operatives times may represent a limitation especially in high risk patients.